Sorafenib in combination with capecitabine: an oral regimen for patients with HER2-negative locally advanced or metastatic breast cancer.

PURPOSE: Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) -negative breast cancer. PATIENTS AND METHODS: Patients were randomly assigned to first- or second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS). RESULTS: In total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand- foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively). CONCLUSION: Addition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose.

One year experience of a model for melanoma continuous prevention in the city of Jaú (São Paulo), Brazil.

BACKGROUND: Worldwide incidence of melanoma has increased in recent years faster than any other cancer. Although it represents only 4% of skin cancers it is nevertheless responsible for 60% of skin cancer deaths. This makes melanoma a public health problem. OBJECTIVES: The aim of this study was the development of a continuous program for melanoma prevention and early detection. METHODS: A city of around 130,000 inhabitants in the state of São Paulo, Brazil, was chosen for the development of a pilot project covering primary prevention and early diagnosis of melanoma. A nursing team worked for approximately 30 days in each of the 13 health centers in the city of Jaú (SP), providing guidance on self-examination of the skin, photoprotection and recognition of early signs of melanoma. Patients with suspicious lesions were immediately sent to the reference hospital for medical and dermoscopic screening. Excisional biopsies were performed on suspected melanomas. RESULTS: 4 four cases of early stage melanoma and 3 dysplastic nevi were diagnosed. Of the people interviewed, 74% worked either part-time or full-time exposed to sun and over 60% claimed to never use sunscreen. CONCLUSION: This is a new and effective model for melanoma prevention and early diagnosis. In short, the melanoma prevention program is able to quickly identify suspicious lesions, leading to early diagnosis and better chances of survival.

Experiência de um ano de modelo de programa de prevenção contínua do melanoma na cidade de Jaú-SP, Brasil / One year experience of a model for melanoma continuous prevention in the city of Jaú (São Paulo), Brazil

FUNDAMENTO: A incidência do melanoma aumentou nos últimos anos mais rapidamente do que qualquer outro câncer. Embora represente apenas 4 por cento dos cânceres de pele, é o responsável por 60 por cento das mortes por esta neoplasia. Isto torna o melanoma um problema de saúde pública. OBJETIVOS: O presente estudo propôs o desenvolvimento de um Programa Contínuo de Prevenção do Melanoma, por meio da realização da prevenção primária e do diagnóstico precoce desta neoplasia. MÉTODOS: Foi tomada como piloto uma cidade de aproximadamente 130.000 habitantes. Uma equipe de enfermagem esteve presente por cerca de 30 dias em cada um dos 13 postos de saúde da cidade de Jaú (SP), realizando orientações quanto ao autoexame da pele, fotoproteção e sinais precoces do melanoma. O paciente com lesão suspeita era encaminhado imediatamente ao hospital de referência para dermatoscopia e triagem médica, sendo excisada quando suspeita. RESULTADOS: Foram diagnosticados 4 casos de melanoma em fase inicial e 3 nevos displásicos. Dos entrevistados, 74 por cento trabalham expostos ao sol, variando de meio período ao completo, e mais de 60 por cento nunca fizeram uso de filtro solar. CONCLUSÃO: Este modelo de programa de prevenção é inédito, exclusivo e demonstrou ser eficaz na prevenção e diagnóstico precoce do melanoma em uma cidade de 130.000 habitantes do Estado de São Paulo. Com esclarecimento à população e orientação à equipe de saúde, realiza-se uma rápida triagem e identificam-se lesões suspeitas de melanoma para que, com o diagnóstico em suas fases iniciais, o paciente apresente melhor prognóstico.

BACKGROUND: Worldwide incidence of melanoma has increased in recent years faster than any other cancer. Although it represents only 4 percent of skin cancers it is nevertheless responsible for 60 percent of skin cancer deaths. This makes melanoma a public health problem. OBJECTIVES: The aim of this study was the development of a continuous program for melanoma prevention and early detection. METHODS: A city of around 130,000 inhabitants in the state of São Paulo, Brazil, was chosen for the development of a pilot project covering primary prevention and early diagnosis of melanoma. A nursing team worked for approximately 30 days in each of the 13 health centers in the city of Jaú (SP), providing guidance on self-examination of the skin, photoprotection and recognition of early signs of melanoma. Patients with suspicious lesions were immediately sent to the reference hospital for medical and dermoscopic screening. Excisional biopsies were performed on suspected melanomas. RESULTS: 4 four cases of early stage melanoma and 3 dysplastic nevi were diagnosed. Of the people interviewed, 74 percent worked either part-time or full-time exposed to sun and over 60 percent claimed to never use sunscreen. CONCLUSION: This is a new and effective model for melanoma prevention and early diagnosis. In short, the melanoma prevention program is able to quickly identify suspicious lesions, leading to early diagnosis and better chances of survival.

Prognostic and risk factors in patients with locally advanced cutaneous squamous cell carcinoma of the trunk and extremities.

55 patients with advanced cutaneous squamous cell carcinoma (CSCC) of the trunk and extremities were studied. A Tissue Microarray was constructed using immunohistochemistry to quantify expression of the HER family, E-cadherins, and podoplanin. Clinical and histopathological factors related to lymph node metastasis and prognosis were also established. Primary tumor positivity was 25.5% for EGFR, 87.3% for HER-3, and 48.1% for HER-4. Metastases were positive for EGFR in 41.7%, for HER-3 in 83.3%, and HER-4 in 43.5%. HER-2 was negative in all samples. Membrane E-cadherin and cytoplasmic E-cadherin were positive in 47.3% and 30.2% of primary tumors and 45.5% and 27.3% of metastases, respectively. Podoplanin was positive in 41.8% of primary tumors and 41.7% of metastases. Intratumoral lymphocytic infiltrate was associated with lymph node metastasis. Patients with T3 tumors had better cancer-specific survival (CSS) than those with T4 tumors; patients with no lymph node involvement had better CSS than patients with N1 tumors. Undifferentiated tumors and hyperexpression of podoplanin were negative prognostic indicators on multivariate analysis.

Registro de câncer de base populacional de Jaú, SP, 2000 a 2004 / Cancer registry population-based Jau, SP, 2000 to 2004

Os dados referentes às pessoas residentes no município e com diagnóstico confirmado entre janeiro de 2000 e dezembro de 2004 já foram coletados e brevemente serão divulgados através de uma publicação específica. Atualmente estão sendo coletados os dados do período janeiro/2005 a dezembro/2008.São registros que nos fornecem informações permanentes sobre o número de casos novos nessa área delimitada, permitindo detectar setores onde a população local é mais afetada pela doença, fatores ambientais que possam estar relacionados e influenciar na prevalência da doença, identificar grupos étnicos afetados promovendo assim investigações epidemiológicas e estudos específicos. As informações obtidas desses registros também auxiliam na determinação da necessidade de campanhas junto à população na detecção precoce e prevenção do câncer, como também na avaliação de novas técnicas diagnósticas.

Linfangiomatose retroperitoneal / Retroperitoneal lymphangiomatosis

Um caso raro de linfangiomatose envolvendo unilateralmente o retroperitôneo, canal femural e rim ipsilateral é relatado. As características clínicas e formas de tratamento säo revistas.